The proposed research involves the molecular recognition of DNA duplexes mediated by two types of metal complexes. One is a ruthenium chiral propeller major-groove binder, and the second is a crescent structure with a pseudocrown ether and two netropsin arms, which binds in the minor groove and is metalloregulated by the divalent cations barium or strontium. The unique capabilities of high-field, high-resolution nuclear magnetic resonance (NMR) will be used to examine structural and dynamic aspects of the binding to specific short DNA duplexes and to test the model for binding proposed by Dervan and co-workers who designed and synthesized this crescent complex and identified its dimeric binding site '5-TATAGGTTAA-3' and its complementary strand. The 1"1 combination of the crescent complex and its binding site will be prepared and investigated by 1-D and 2D-FT- NMR. The component species of this duplex complex will be custom synthesized. Various ruthenium propeller complexes will be tested for binding and intercalation into DNA. Their chiral recognition aspects will be tested by binding studies with DNA of known helical family (A, B, or Z). After other physical-chemical and biochemical techniques have been used to study DNA binding specificity by these metal complexes, NMR studies will again be used to probe the subtelties of DNA binding and the effect of base pair sequence on helix geometry. The long-range goal and health related aspects of the project are to better understand (at the level of interaction of specific atoms) the binding of substances to DNA in both the major and minor groove.